The ultimate objective is to identify environmental factors and physiologic states, of relevance to humans, whereby toxic levels of aluminum are able to breach the normal barriers and gain entrance to the nervous system. The specific long-term objective of this study is to determine whether factors exist, under naturally occurring conditions, whereby dietary aluminum is able to breach the gut-epithelial barrier and blood-brain-barrier in sufficient quantity to produce toxicity of the nervous system, using the rabbit as a model. To accomplish this, it is necesary to test these barriers individually. This will entail use of agents which, based on preliminary data, are postulated to have an enhancing effect on dietary aluminum absorption. The specific objectives are: 1. To determine whether or not a relationship exists between continuous calcitriol (1,25(OH)2D3) and parathyroid hormone administration (by Alzet osmotic pump) and subsequent levels of serum and bone aluminum (thus demonstrating whether or not these agents enable dietary aluminum to breach the gut-epithelial barrier). 2. To determine whether or not the incomplete blood-brain-barrier of the fetus permits aluminum from elevated plasma aluminum from the pregnant dam (or via the milk aluminum in the neonate) to breach this barrier in the neonatal brain. 3. To determine the risk of aluminum-induced encephalopathy in adult and neonatal rabbits exposed to high dietary aluminum under the above conditions. 4. To describe and define the morphologic and chemical changes in the nervous system of animals under the above regimens, utilizing techniques of silver carbonate impregnation; transmission (TEM) and scanning transmission (STEM) electron microscopy; X-ray microanalysis for aluminum, and serum and brain tissue quantitative aluminum analayis by atomic absorption spectroscopy. The information obtained from the above studies should contribute to the understanding of the significance of aluminum in certain encephalopathies of humans, including dialysis dementia and Alzheimer disease. It would also provide some comparative insight into the recently described aluminum loading in infants receiving intravenous therapy. This model, once developed, should facilitate the correlation of aluminum-induced neuronal degenerations with abnormalities of cholinergic function.